Eli-cel Gene Therapy for Early CALD to Be Withdrawn From EU, UK

bluebird bio is withdrawing its EU marketing authorization and UK filing for Skysona (elivaldogene autotemcel; eli-cel) for the treatment of cerebral adrenoleukodystrophy (CALD), the company revealed in a recent securities and exchange commission filing.¹

The company also plans to withdraw Zynteglo (betibeglogene autotemcel; beti-cel) for the treatment of beta-thalassemia from both markets by early 2022. bluebird previously withdrew beti-cel from Germany due to price and marketing disputes and also reduced their workforce there.² These moves come after the company’s previous announcement of restructuring to focus on US operations and scale back EU operations. At that time, bluebird also announced that they were seeking a licensing agreement to continue access to their therapies in the EU.

When bluebird announced reducing operations in Germany, Andrew Obenshain, president, severe genetic diseases, bluebird bio, said in a statement that “In terms of operations, we have faced challenges over the last year that have resulted in the difficult decision to reduce our workforce and say goodbye to some valued bluebirds. We want to express our gratitude for their contributions and commitment to patients. As we move into the future, we look forward to bluebird bio advancing as a strong, thriving organization that is dedicated to developing treatments for rare genetic diseases."²

READ MORE: Addressing Adverse Events in Gene Therapy

In the filling, bluebird stated that they will continue long-term follow-up of patients previously enrolled in European clinical trials but will not initiate any new programs for beta-thalassemia, CALD, or sickle cell disease gene therapies.

The EMA only approved eli-cel in July 2021 for pediatric patients with early CALD with an ABCD1 mutation and no matched sibling donors.³ At the time of the approval, bluebird was planning to submit a biologics license application (BLA) for the therapy in the US, however, the FDA placed a clinical hold on the program in August 2021 after a participant developed a Suspected Unexpected Serious Adverse Reaction (SUSAR) of myelodysplastic syndrome (MDS) thought to be mediated by the use of their lentiviral vector.⁴

“Given what we know, we remain confident that eli-cel can offer hope for patients and families impacted by this devastating disease who have very few treatment options. We are committed to working with regulators and physicians in order to resolve this hold as soon as possible and bring this important therapy to patients in need,” Nick Leschly, president and chief executive officer, bluebird, previously said in a company update.⁴ 

While the eli-cel program remains on clinical hold, bluebird did submit a BLA for beti-cel in September 2021 for patients with β-thalassemia who require regular red blood cell transfusions.⁵ The submission as based on data from 2 phase 3 studies (NCT03207009 and NCT02906202) evaluating beti-cel across all phenotypes as well as a previous phase 1/2 study (NCT01745120). The compiled data comprise over 220 patient years of beti-cel treatment.

"With this submission, we are one step closer to bringing a potentially transformative gene therapy to people living with TDT and their families," Obenshain said in a statement at that time.⁵ "At bluebird bio, we have a deep understanding of gene therapies, built over a decade of research and development in severe genetic diseases. We look forward to working with the FDA on its review of this BLA as we realize the promise that one-time gene therapies hold for patients."

REFERENCES

1. bluebird bio. Form 8-K. October 21, 2021. https://investor.bluebirdbio.com/node/14816/html
2. bluebird to withdraw Zynteglo from Germany after price negotiations failed to recognize drug’s value. News release. April 24, 2021. Accessed October 25, 2021. https://www.eversana.com/2021/04/21/bluebird-to-withdraw-zynteglo-from-germany-after-price-negotiations-failed-to-recognize-drugs-value/
3. bluebird bio receives EC approval for SKYSONA™ (elivaldogene autotemcel, Lenti-D™) gene therapy for patients less than 18 years of age with early cerebral adrenoleukodystrophy (CALD) without matched sibling donor. News release. bluebird bio. July 21, 2021. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-receives-ec-approval-skysonatm-elivaldogene
4. bluebird bio reports second quarter financial results and provides operational update. News release. bluebird bio. August 9, 2021. https://www.businesswire.com/news/home/20210809005334/en/bluebird-bio-Reports-Second-Quarter-Financial-Results-and-Provides-Operational-Update
5. bluebird bio submits biologics license application (BLA) to FDA for betibeglogene autotemcel (beti-cel) gene therapy for patients with β-thalassemia who require regular red blood cell transfusions. News release. bluebird bio. September 21, 2021. https://www.businesswire.com/news/home/20210921005978/en/bluebird-bio-Submits-Biologics-License-Application-BLA-to-FDA-for-betibeglogene-autotemcel-beti-cel-Gene-Therapy-for-Patients-With-%CE%B2-thalassemia-Who-Require-Regular-Red-Blood-Cell-Transfusions